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The investigators conduct a single-center, prospective, observational study to explore the value of EUS-guided portal vein circulating tumor cells (PV-CTCs) and their subtypes combined with multi-omics tests in the early warning of recurrence and metastasis of resectable pancreatic cancer(RPC) and borderline resectable pancreatic cancer (BRPC).
A total of 20 participants are stratified based on imaging studies into the resectable pancreatic cancer group (8 cases), the borderline resectable pancreatic cancer group (8 cases), and the locally advanced pancreatic cancer group (4 cases). These patients have solid space-occupying lesions (with a diameter >1cm) within the accessible range of endoscopic ultrasound (EUS) for the pancreas as indicated by imaging studies. Every trial patient will get a unique identification number, and it will not change through out the whole trial.
Use the inclusion and exclusion criteria to observe the patients and do relative inspections, and confirm if the patients qualified or not to the trial. Record the result of last time test before the treatment. Although it is better to get the informed consent before doing all kinds of observation and tests, if for some reason, the medical imaging examination has completed, as long as the imaging examination was done within 3 weeks before the needle biopsy, it can still be collect as baseline data; other lab test items done at 2 weeks before the needle biopsy can still be collect as baseline data for pre-research use, but these tests should be done at the trail center hospital so as to guarantee the data trace ability.
The investigators will do the sampling procedures for all of them in a strict sequence: first, under EUS guidance, 10ml of portal vein blood is prioritized for collection using a 22G ECHO 3-22 needle to avoid contamination. Subsequently, the investigators will do the needle passes for 3 times on the pancreatic lesion with 5 mL wet suction for tissue acquisition. Finally, 10ml of peripheral blood is collected. Samples are processed using CTC100 system or IFC-IMP technology, followed by scRNA-seq (10xGenomics) and proteomic analysis (timstofPro2/orbitrap). The results will be fed back to clinicians within 3 working days. Without knowing the sample source (blinded to specific subtypes initially), the cytologist and pathologist evaluate the specimen quality and make diagnosis.
Follow up (outpatient follow up or telephone follow up) the patients at 1 week, 12 weeks and 36 weeks after the puncture and collect the patients clinical data and confirm their final diagnosis.
During the trial, if severe adverse event occurs, the trialed center must take immediate actions necessary to guarantee the trialed patients' safety. Once severe adverse event occurs, the researchers should inform the trial applicant and the trail center's ethics committee within 24 hours after the researchers gets to know the adverse event. And the researchers should also fax the report to State Food and Drug Administration of China and the local provincial food and drug administration. After receiving the report, the applicant should inform other clinical trial centers within 24 hours. All the severe adverse events should be filed at group leader medical center and other trial centers.
Case Report Form (CRF ) will be filled by the researchers, every involved patient must have the CRF filled. This will be audited by clinical monitor and handed over to data administrator to input and manage data, the first copy will be kept by the applicant, the second copy will go to the trial center, and the third copy will be kept by the trail researchers. The data input and management will be taken care by specially assigned person. In order to guarantee the data accuracy, data input will be done twice by two independent data administrators, by computerized and manual verifying, hand over the data to statistical experts to do check and statistic analyzing.
For the questions and doubts within the case report form, the data administrator make Data Resolution Query (DRQ) and via the clinical monitor asking the researchers. The researchers will answer and feed back as soon as possible. According to the researchers answer, data administrator will do the data modifying, confirming or inputting, and when necessary send out DRQ again.
This will be done by specialized statistic analyzing people according to the predetermined statistic analyzing plan. The statistic analyze will be carried out according to intention principle confirmed full analysis set and per-protocol set principle. After completing the statistic analyzing, the statistic analyzer issue the statistic analysis report and send this to major researchers to write the study report.
Statistic analyzing plan: ⑴ General principle: ①all the statistic tests are use the two-tailed-test method, P<0.05 will be thought as the tested difference is statistical significance. ② the quantitative indicator description will calculate the Mean and Standard deviation. The classification indicator description will describe the cases and percentage of all types of cases. ⑵ Statistic analyzing method: ①for the measurement data, compare the difference between Portal Vein CTCs and Peripheral Blood CTCs, use paired t-test or symbol rank sum test to compare with the difference within the group. ② for the counting data (CTC subtypes), use x2 test or Fisher's exact test method to compare the groups. ⑶ Shedding analysis: Comparison of groups' total shedding rates and the shedding rates caused by adverse events will use x2 test or Fisher's exact test method. ⑷ The baseline value's equilibrium analysis: Use group t test or x2 test to compare the demography info and vital signs, disease history, and basic treatment and other indicators of baseline value, so as to measure the balance of the groups. ⑸ Effectiveness analysis: The major indicator of effectiveness analysis is the correlation between PV-CTC quantity/subtypes and the recurrence/metastasis of BRPC, and the indicators of second effectiveness include the applicability of neoadjuvant therapy guidance. ⑹ Safety analysis: Use x2 test or Fisher's exact test to compare the adverse event/adverse reaction (include puncture complications like pancreatitis, bleeding) rates. And use table to describe the adverse events during this trial project; the lab test results before and after the trial, the normal/abnormal changing condition and the relationship with this trial research when abnormal changes happened.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RPC | Patients diagnosed with resectable pancreatic cancer by imaging (CT/MRI) |
| |
| BRPC | Patients diagnosed with borderline resectable pancreatic cancer by imaging (CT/MRI) |
| |
| LAPC | Patients diagnosed with locally advanced pancreatic cancer by imaging (CT/MRI) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CTC | Diagnostic Test | Obtaining portal vein blood and peripheral blood from patients, extracting circulating tumor cells (CTCs) therein, and performing CTC sorting, thereby assisting clinical evaluation of the applicability of neoadjuvant therapy and prognostic assessment for patients with potentially resectable pancreatic cancer. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of circulating tumor cells in the portal vein | Explore the value of the number of circulating tumor cells in the portal vein in evaluating the applicability of neoadjuvant therapy and guiding treatment decisions for BRPC patients | Up to 24 months |
| Subpopulation classification of portal vein circulating tumor cells | Explore the application of portal vein circulating tumor cell subset classification in the prognostic evaluation of neoadjuvant therapy in BRPC patients | Up to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Subgroup Classification of Portal Vein Circulating Tumor Cells (PV-CTCs) and Peripheral Blood Circulating Tumor Cells (PB-CTCs) | Explore the differences in subpopulation classification between portal vein circulating tumor cells (PV-CTCs) and peripheral blood circulating tumor cells (PB-CTCs), and investigate their roles in the process of liver metastasis of pancreatic cancer. | Up to 24 months |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with pancreatic cancer from Tongji Hospital, Wuhan, scheduled for ultrasound-guided fine-needle aspiration biopsy
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Bin Cheng | Contact | +8613986097542 | b.cheng@tjh.tjmu.edu.cn | |
| Qingxiong Ma | Contact | 13588580316 | u202110372@hust.edu.cn |
| Name | Affiliation | Role |
|---|---|---|
| Bin Cheng | Tongji Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tongji Hospital, Tongji Medical College, HUST | Wuhan | Hubei | 430030 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28338171 | Result | Chen L, Chen M, Chen J. [Advances of circulating biomarkers in gastroenteropancreatic neuroendocrine neoplasms]. Zhonghua Wei Chang Wai Ke Za Zhi. 2017 Mar 25;20(3):357-360. Chinese. | |
| 26341722 | Result | Catenacci DV, Chapman CG, Xu P, Koons A, Konda VJ, Siddiqui UD, Waxman I. Acquisition of Portal Venous Circulating Tumor Cells From Patients With Pancreaticobiliary Cancers by Endoscopic Ultrasound. Gastroenterology. 2015 Dec;149(7):1794-1803.e4. doi: 10.1053/j.gastro.2015.08.050. Epub 2015 Sep 2. |
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| ID | Term |
|---|---|
| D010190 | Pancreatic Neoplasms |
| D012008 | Recurrence |
| D009362 | Neoplasm Metastasis |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
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portal vein blood & peripheral blood
|
| 38628105 | Result | Wang JX, Lu LG, Cai XB. Endoscopic ultrasound for the diagnosis and treatment of primary hepatocellular carcinoma. J Dig Dis. 2024 Mar;25(3):156-162. doi: 10.1111/1751-2980.13266. Epub 2024 Apr 17. |
| 38781696 | Result | Zhu Z, Zhang Y, Zhang W, Tang D, Zhang S, Wang L, Zou X, Ni Z, Zhang S, Lv Y, Xiang N. High-throughput enrichment of portal venous circulating tumor cells for highly sensitive diagnosis of CA19-9-negative pancreatic cancer patients using inertial microfluidics. Biosens Bioelectron. 2024 Sep 1;259:116411. doi: 10.1016/j.bios.2024.116411. Epub 2024 May 20. |
| 34256456 | Result | Chinese Pancreatic Surgery Association, Chinese Society of Surgery, Chinese Medical Association. [Guidelines for the diagnosis and treatment of pancreatic cancer in China(2021)]. Zhonghua Wai Ke Za Zhi. 2021 Jul 1;59(7):561-577. doi: 10.3760/cma.j.cn112139-20210416-00171. Chinese. |
| 34547082 | Result | Park W, Chawla A, O'Reilly EM. Pancreatic Cancer: A Review. JAMA. 2021 Sep 7;326(9):851-862. doi: 10.1001/jama.2021.13027. |
| 29113659 | Result | Ielpo B, Caruso R, Duran H, Diaz E, Fabra I, Malave L, Ferri V, Alvarez R, Cubillo A, Plaza C, Lazzaro S, Kalivaci D, Quijano Y, Vicente E. A comparative study of neoadjuvant treatment with gemcitabine plus nab-paclitaxel versus surgery first for pancreatic adenocarcinoma. Surg Oncol. 2017 Dec;26(4):402-410. doi: 10.1016/j.suronc.2017.08.003. Epub 2017 Aug 24. |
| 31892339 | Result | Pan L, Fang J, Tong C, Chen M, Zhang B, Juengpanich S, Wang Y, Cai X. Survival benefits of neoadjuvant chemo(radio)therapy versus surgery first in patients with resectable or borderline resectable pancreatic cancer: a systematic review and meta-analysis. World J Surg Oncol. 2019 Dec 31;18(1):1. doi: 10.1186/s12957-019-1767-5. |
| 33934960 | Result | Crippa S, Belfiori G, Bissolati M, Partelli S, Pagnanelli M, Tamburrino D, Gasparini G, Rubini C, Zamboni G, Falconi M. Recurrence after surgical resection of pancreatic cancer: the importance of postoperative complications beyond tumor biology. HPB (Oxford). 2021 Nov;23(11):1666-1673. doi: 10.1016/j.hpb.2021.04.004. Epub 2021 Apr 20. |
| D004066 |
| Digestive System Diseases |
| D010182 | Pancreatic Diseases |
| D004700 | Endocrine System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009385 | Neoplastic Processes |